THE HUMAN GENOME PROJECT: IMPLICATIONS FOR HEALTH CARE, RESEARCH AND SOCIETY

1. THE HUMAN GENOME PROJECT: IMPLICATIONS FOR HEALTH CARE, RESEARCH AND SOCIETY Washington, DC March 25, 2002 Alan E. Guttmacher, M.D. National Human Genome Research Institute National Institutes of Health

2. What We Will Consider • “Traditional genetics” • The Human Genome Project • The “new genetics” - genomics • Genomic health care • Genomics and society • Genomics and research

3. “Traditional Genetics” • Involves conditions wholly caused by: • An extra or missing complete chromosome or part of a chromosome • e.g., Down syndrome • A mutation in a single gene • e.g., cystic fibrosis, fragile-x syndrome, sickle cell disease

4. “Traditional Genetics” • These conditions • Are of great importance to individuals and families with them • But, even when added together, are relatively rare • Most people not directly affected • Thus, genetics played small role in health care (and in society)

5. > 9 of the 10 Leading Causes of Mortality Have Genetic Components • 1. Heart disease (29.5% of deaths in ‘00) • 2. Cancer (22.9%) • 3. Cerebrovascular diseases (6.9%) • 4. Chronic lower respiratory dis. (5.1%) • 5. Injury (3.9%) • 6. Diabetes (2.9%) • 7. Pneumonia/Influenza (2.8%) • 8. Alzheimer disease (2.0%) • 9. Kidney disease (1.6%) • 10. Septicemia (1.3%)

6. Genomic Medicine • Will come largely from knowledge emanating from the Human Genome Project

7. The Human Genome Project • An international government project that is ahead of schedule! • And under budget!! • And from its start has earmarked funds for consideration of its ethical, legal, and social implications (ELSI) - the largest funding ever devoted to bioethics!!!

8. The Human Genome Project • Human genome consists of three billion base pairs – Adenine, Cytosine, Guanine, Thymine • Printing out the A,C,G,T would fill over 150,000 telephone book pages • Disease is often caused by a single variation in the three billion bases - one letter in 150,000 pages different

9. Human Genome Project - Sequence Progress (12/31/01) Draft = 34.8% Finished = 63.0% Total = 97.8%

10. Genomic Medicine • About conditions partly: • Caused by mutation(s) in gene(s) • e.g., breast cancer, colon cancer, atherosclerosis, inflammatory bowel disease, diabetes, Alzheimer disease, mood disorders, many others • Prevented by mutation(s) in gene(s) • e.g., HIV (CCR5), ?atherosclerosis, ?cancers, ?diabetes, many others

11. Genomic Medicine • These conditions • Are also of great importance to individuals and families with them • But are quite common • Directly affect virtually everyone • Will make genetics play large role in health care and in society

12. Genomic Medicine • These conditions are common enough that: • Genetics care will be supplied with occasional involvement of medical geneticists and genetic counselors, but primarily by primary care providers and other non-genetics specialists

13. Genomic Medicine • Will change health care by... • Creating a fundamental understanding of the biology of many diseases, even many “non-genetic” ones • Leading to defining disorders by mechanism of causation, rather than by symptoms

14. Genomic Medicine • Will change health care by... • providing knowledge of individual genetic predispositions • creating pharmacogenomics

15. Genomic Medicine • Knowledge of individual genetic predispositions will allow: • Individualized screening • Individualized behavior changes • Presymptomatic medical therapies, e.g., antihypertensive agents before hypertension develops, anti-colon cancer agents before cancer occurs

16. Genomic Medicine • Pharmacogenomics will allow: • new approaches to drug design • individualized medication use based on genetically determined variation in effects and side effects • new medications for specific genotypic disease subtypes

17. Genomic Medicine • Will change health care by... • providing better understanding of non-genetic (environmental) factors in health and disease • allowing genetic engineering • emphasizing health maintenance rather than disease treatment

18. The “New Genetics” • Will include knowledge about traits that most of us see as human characteristics, rather than as “diseases” • e.g., height, intelligence, alcoholism, violence, etc.

19. The “New Genetics” • Will also change our lives… • Knowing our own (and others’) disease predispositions • Knowing our (and others’) “characteristics” predispositions • Showing that we are all mutants

20. The “New Genetics” • May also change society… • Genetic stratification, e.g., in employment or marriage • Genetic engineering against (and for) diseases and characteristics • Cloning • Increased opportunity for “private eugenics”

21. The “New Genetics” • Raises new concerns, such as: • Discrimination against individuals • Discrimination against groups • Nature over nurture? (genetic determinism) • Genes run in families • Confidentiality/privacy

22. The “New Genetics” • And more concerns, such as: • Fairness in access • Right not to know and not to act • What is the appropriate informed consent process for genetic testing • Patenting and licensing

23. Areas of Genomics Related Research • Model organisms • Annotation of the genome • Proteomics • Biological pathways, networks, cellular mechanisms, etc. • New technologies • Pathophysiology of disease

24. Areas of Genomics Related Research • Gene-gene-environment interactions • Pharmaceutical design and use • Health outcomes • Health care delivery • Ethical, legal and social issues • Etc., etc.